16. Sensory and motor processing: Mechanisms underlying sensory processing in the aging nervous system. The P.I. is an investigator who has not done research on the aging nervous system before. Nerve injury often causes a condition called neuropathic pain in which increased sensitivity to thermal and mechanical stimuli develops. The prevalence of neuropathic pain increases with age, yet most of the research on the condition uses young rats. One model that was developed in rats to mimic this condition in humans is that of Bennett and Xie (1988): a sciatic nerve is loosely ligated and the rat develops a sensitivity to touch and to temperature (hyperalgesia) on that side. At least part of the sensitivity that develops is due to changes in the spinal cord. A key chemical in the processing of pain information in the spinal cord is substance P (SP), which is released from sensory nerve fibers during noxious stimulation. The hypothesis to be tested is that the increased sensitivity to pain seen with aging is due, at least partially, to increases in amounts of of the SP receptor, neurokinin-1 (NK-1) in the spinal cord. The amount of SP in the spinal cord decreases with age. The decrease in SP may result in an up-regulation of its receptor, NK-1, leading to increased sensitivity to pain in aged rats, similar to that seen in certain chronic painful conditions in humans. The effect of age on NK-1 receptor amounts and internalization in normal rats and in rats with neuropathic pain will be investigated. These changes will be correlated with development of behavioral sensitivity to thermal stimuli. Neuropathic pain is very difficult to alleviate because it does not respond to treatment with commonly used analgesics. Information on central nervous system changes (morphological and chemical) underlying this condition are key to developing effective treatments. There is evidence that young and aged animals differ in their responses to nerve injury. Thus it is important that experiments on neuropathic pain be done on aged rats. The investigators on this grant are two neurobiologists and a phamacologist who are interested in central nervous system changes that occur with injury. The long term goals of the investigators are to study neuropathic pain in aged animals so that we have a better basis on which to design treatments for this condition.